We have recently described a new biological phenomenon, we have termed mesenchymal-endothelial- transition (MEndoT), where scar forming cells in the heart, exhibit plasticity and adopt endothelial cell like fates after cardiac injury. Fibroblast derived endothelial cells contributed to post injury neovascularization and disruption of MEndoT worsened post injury neovascularization and repair. In contrast, augmentation of MEndoT decreased fibrosis and enhanced cardiac repair, demonstrating the potential of MEndoT as a novel therapeutic target in acute heart injury. In more chronic forms of cardiac injury such as cardiac hypertrophy, increased neovascularization is a critical part of the cardiac compensatory response. Enhanced neovascularization is seen in the initial compensatory phase while regression of vasculature and increased fibrosis are seen in the maladaptive phase prior to the development of heart failure. Disruption of neovascularization accelerates and enhanced neovascularization delays or retards the development of heart failure after cardiac hypertrophy. However whether mesenchymal-endothelial-transition occurs in cardiac hypertrophy and can serve as a therapeutic target for delaying or retarding the development of heart failure is not well understood. In this proposal we provide preliminary evidence that mesenchymal-endothelial transition occurs in cardiac hypertrophy and interrogate the physiological role of MEndoT in cardiac hypertrophy with gain and loss of function approaches. Our experiments will provide novel insight into the physiological role of MEndoT in cardiac hypertrophy and potentially identify MEndoT as a novel target for retarding heart failure secondary to cardiac hypertrophy.